Altered p-STAT3 (tyr705) expression is associated with histological grading and intratumour microvessel density in hepatocellular carcinoma

Abstract

Background: Constitutive activation of signal transducer and activator of transcription 3 at tyrosine residue 705 (p-STAT3 (tyr705)) has been associated with many types of human cancers. However, its potential roles and biological effects in hepatocellular carcinoma (HCC) are not well established. Aim: To explore whether an altered p-STAT3 (tyr705) expression is associated with angiogenesis or proliferation and thereby plays a part in HCC development. Methods: Paraffin-wax-embedded sections from 69 patients with HCC were collected in this study. Using a semiquantitative immunohistochemical staining method, the expression patterns of p-STAT3 (tyr705) in both HCC lesions and the adjacent non-tumorous liver parenchyma were analysed. The results obtained were further correlated with intratumour microvessel density (MVD), Ki-67 expression, clinicopathological parameters and overall survival. Results: A strong p-STAT3 (tyr705) nuclear staining was observed in 49.3% of HCC lesions, but was reported only in 5.8% of the adjacent non-tumorous liver parenchyma (p,0.001). The expression of p-STAT3 (tyr705) in HCC lesions was significantly and positively correlated with the intratumour MVD (p = 0.002), but not with Ki-67 expression. No significant correlation of p-STAT3 (tyr705) was found in addition to histological grading (p = 0.019). Multivariate Cox regression analysis showed that p-STAT3 (tyr705) expression was a significant predictor of overall survival for HCC (p = 0.036), although the Kaplan-Meier survival curves showed no significant difference between the high and low p-STAT3 (tyr705) expression subgroups. Conclusions:The results showed that p-STAT3 (tyr705) expression was closely correlated with histological grading and intratumour MVD in HCC. Thus, the potential role of p-STAT3 (tyr705) in HCC development may be through these correlations.

Potential role of signal transducer and activator of transcription (STAT)3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma

“…Elevated STAT3 and p705 STAT3 expression in HCC tissue has also been reported [120]. Recent data also indicate an association of pSTAT3 with the histological grade of HCC tissue from 67 patients [201]. When anti-cancer small molecule S3I-201 was administered at a dose of 5 mg/kg every other day to xenografts of the human HCC cell line HUH-7, it was found that S3I-201 inhibited STAT3 tyrosine phosphorylation and tumor growth [6].…”

Macrophage-secreted IL-8 induces epithelial-mesenchymal transition in hepatocellular carcinoma cells by activating the JAK2/STAT3/Snail pathway

“…STAT3 is regarded as a critical transcription activator for cell cycle or cell survival-related genes, and its phosphorylation has been linked to HCC tumor progression (42), angiogenesis (43) and tumorigenesis (44). Colomiere et al (45) have reported that activation of the JAK2/STAT3 pathway may result in EMT-associated phenotypes of ovarian cancer cells.…”

Prognostic significance of phosphorylated signal transducer and activator of transcription 3 and suppressor of cytokine signaling 3 expression in hepatocellular carcinoma

“…Among the STAT family members, activated STAT3 plays a vital role in a diverse group of human cancers. Yang et al (9) detected pSTAT3 expression in 69 HCC and corresponding adjacent non-tumor parenchyma by immunohistochemistry, and found that 49.3% of HCC and 5.8% of non-tumorous tissues were positive for pSTAT3 nuclear staining. This observation differed quantitatively, but not qualitatively with our observation that pSTAT3-positive expression was observed in 54.3% of HCC and 31.8% of non-tumor tissues.…”